Immunisation of pregnant women with acellular Bordetella pertussis vaccine.

Bordetella pertussis, the causative agent of whooping cough, can cause severe
disease in infants too young to be vaccinated or who have not completed the
primary series. In complete vaccination, 100% protection is reached after 4 to
5 months (1).
Despite vaccination the incidence of whooping cough is rising the last decade
with the highest infection-frequency in adolescents and young adults. The
latter can be an important source of infection to infants less than 4 to 5
months old. Maternal immunization offers the possibility to protect these
infants from birth until immunity is achieved by active vaccination this has
proven to be effective in tetanus and influenza. Several studies indicated that
maternal immunization against B. pertussis may be effective (2). For the
development of a vaccination programme against B. pertussis in pregnant women
knowledge is needed about the antibody-response in mother and child after
maternal vaccination.

1) To test the feasibility of vaccinating pregnant women against B. pertussis
in preventing B. pertussis infection in newborn babies.
2) To test the safety of vaccinating pregnant women against B. pertussis in
preventing B. pertussis infection in newborn babies.

A prospective cohort study.
Part 1: Immunization of pregnant women in the third trimester of pregnancy with
an acellular pertussis vaccine. Blood samples will be drawn to study antibody
responses.

Part 2: Blood samples of infants of mothers vaccinated during pregnancy in part
1 will be drawn to study antibody responses.

The study group will receive an DTaP-IPV booster vaccine, with reduced D and
monovalent aP content vaccine during the third trimester of pregnancy.

Pregnant women are vaccinated with an acellular vaccine, intramuscularly,
during the third trimester of pregnancy by an experienced nurse. Blood samples
will be taken before vaccination, at delivery and at 2 months post-partum.
Participants will be visited for all blood sampling by experienced study nurses
at home to minimize distress. A questionnaire will be handed out to these women
to gain insight in previous immunization and suspected whooping cough.
From infants of mothers included in the study blood will be drawn from the
umbilical cord at delivery and by capillary heel prick tests at 2 month post
partum (before their first vaccination) and 1 month after the 1st, 3rd and 4th
vaccination (vaccinations at 2,3,4 and 11 months). These capillary tests are
less invasive than venous blood sampling.
Based on an extensive literature review (3-8) the estimated risk for the
participants in this study is minimal.

Side-effects that were associated with vigorous serum antibody responses are:
pain, tenderness, induration or erythema at the site of injection (18).
According to recommendations of the US Advisory Committee on immunization
practices (ACIP), pregnancy is not a contraindication for vaccination with
adult formulations of a combined tetanus, diphtheria, acellular pertussis
vaccine. Data on safety, immunogenicity and the outcomes of pregnancy are not
available for pregnant women who receive Tdap. When Tdap is administered during
pregnancy, transplacental maternal antibodies might protect the infant against
pertussis in early life. They also could interfere with the infant's immune
response to infant doses of DTaP, and leave the infant less well protected
against pertussis (9).

The risk and the burden for the subject will be in proportion to the potential
value of the research because we expect that vaccinating pregnant women will
provide protection against B. Pertussis in the neonate directly from birth on.
Hence, complicated infections with B. Pertussis will be prevented.


3) Mooi FR, de Greeff SC. The case for maternal vaccination against pertussis.
Lancet Infect Dis. 2007 ;7:614-624
4) Glezen WP, Alpers M. Maternal immunization. Clin Infect Dis:1999;219-224
5) Kendrick P, Thompson M, Eldering G. Immunity response of mothers and babies
to injections of pertussis vaccine during pregnancy. Am J Dis Childr
1945;70;25-8
6) Lichty JA, Slavin V, Bradford WL. An attempt to increase resistance to
pertussis in newborn infants by immunizing their mothers during pregnancy. J
Clin Invest 1938;17:613-21
7) Cohen P, Scaldron SJ. The placental transmission of protective antibodies
against whooping cough by inoculation of the pregnant women. JAMA
1943;121:656-662
8) Cohen P, Scaldron SJ. The effects of active immunization of the mother upon
the offspring. J Pediatr 1946;29:609-19.
9) http://www.cdc.gov/vaccines/pubs/preg-guide.htm#tdap